Role of testosterone in COVID-19 patients - a double-edged sword?

Hussain, Aneela N.; Hussain, Fazal; Hashmi, Shahrukh K.

COVID-19 affects males twice as frequently as females with significantly increased severity and mortality. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. The gradual decline in total and free testosterone levels has a direct correlation with serious pulmonary complications requiring advanced care (ICU, ventilators, ECMO, etc.). SARS-CoV-2 utilizes Angiotensin-Converting Enzyme II (ACE2) for entry in the host cell, and Transmembrane Protease, Serine 2 (TMPRSS2) to prime spike protein of SARS-CoV-2. Testosterone induces ACE-2 expression, a critical pulmonary protective enzyme. Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome (ARDS, duration of ICU stay, mortality). On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients. A critical evaluation of the serum testosterone and its relevance to COVID-19 is warranted to re-evaluate strategies to effectively triage, prioritize, and manage high-risk patients for ICU admission, survival outcomes, targeted solutions, and operational algorithms.